This application is in response to RFA-CA12-022. It addresses PQD - 2 what molecular properties make some cancers curable with conventional chemotherapy? We choose EBV+ endemic Burkitt lymphoma (BL) as the prototypical cancer that is curable with single agent (cyclophosphamide) in >90% of children. This exceedingly high cure rate was already evident in the 1960s in very limited settings (Uganda) and has since been repeated in the US, in Brazil and other nations. Failure is due to co-factors, including socioeconomically and over all performance score, which limit the patients to complete the prescribed number of cycles, rather than molecular heterogeneity. Hence, the reason that this very aggressive cancer is curable is molecular in nature. We will use a functional genetic approach to understand the molecular properties that render BL susceptible to one of the simplest of chemotherapies.